The goal of this project is the elucidation of information which will lead to an understanding of the role of cerebral RNA and protein metabolism in the mechanisms underlying the development of tolerance to and physical dependence on opiate narcotics. The quantitative, qualitative and temporal changes produced by morphine in protein and mRNA synthesis and degradation in various brain regions will be related to the development of tolerance to the analgesic effect of morphine. Groups of rats (normal, acutely morphinized and morphine tolerant) will be injected with labeled RNA or protein precursors prior to sacrifice. Brains will be dissected into various regions and messenger RNA, ribosomal RNA, free and bound polysomes, nascent polypeptides, amino acids, nucleotides and total RNA and protein will be isolated and analyzed. Techniques of liquid scintillation spectrometry, chromatograph, electrophoresis and sedimentation in sucrose gradients will be employed to analyze populations of macromolecules. These experiments will provide data on the relationship between opiate narcotics and RNA and protein metabolism and how they relate to the development of tolerance. Bibliographic references: Venkatesan, N. and Steele, W.J.: Effects of phenobarbital on protein synthesis anddpolysome levels in rat liver. Chem.-Biol. Interactions. 11: 41-54, 1975. Steele, W.J. and Johannesson, T.: Effects of morphine infusion in maternal rats at near- term on ribosome size distribution in foetal and maternal rat brain. Acta pharmacol. et toxicol. 36: 236-242, 1975.